Peripheral neuropathy is a frequent cause of HIV morbidity. Chronic heavy alcohol use, which itself is one of the two most prevalent causes of peripheral neuropathy, is common in populations at high risk for HIV infection. Chronic heavy alcohol use may effect the Peripheral Nervous System (PNS) morbidity of HIV infection by accelerating the development of immunodeficiency (via biological effects or via effects on treatment seeking and treatment adherence behavior), through interactions between toxic effects or through nutritional deficiency. This project will determine the effects ( and mechanisms underlying these effects) of chronic heavy alcohol use on clinical and functional measures of the Peripheral Nervous System (PNS) morbidity of HIV disease in a 2-year longitudinal study of HIV+ and HIV- chronic heavy drinkers (HIV+HD) and light/non-drinkers (HIV+ L/ND). The Project will: (1) determine whether HIV+ HDs have greater PNS morbidity at baseline than HIV+ L/NDs, (2) determine whether they have a more rapid rate of progression of PNS morbidity than HIV+ L/NDs, (3) determine whether the effects of chronic heavy alcohol use and HIV infection of PNS morbidity at baseline and over the follow-up period are additive or exceed additive effects, and (4) test hypotheses concerning the mechanism(s) for interaction of chronic heavy alcohol use and HIV infection of PNS morbidity and its progression and on the impact of polyneuropathy on clinically important outcomes. Four groups will be studied: 120 HIV+ HDs, 120 HIV+ L/NDs, 60 HIV-HDs, and 60 HIV- L/NDs. PNS function will be measured by clinical exam, quantitative sensory testing, quantitative autonomic testing, and nerve conduction studies. Quantitative sensory deficits will be measured with thermal and vibratory detection thresholds. Quantitative autonomic testing will include heart rate variation to deep breathing and the Valsalva maneuver as well as postural blood pressure testing. Electrophysiological measures will include sensory and motor nerve conduction studies of bilateral lower and non-dominant upper limbs. The establishment of chronic heavy alcohol consumption as a significant co-factor in the pathogenesis of DSP would heighten awareness of health care providers and patients to the importance of this co-factor and would open new therapeutic windows.